Live predator stress in adolescence results in distinct adult behavioral consequences and dorsal diencephalic brain activation patterns.

Exposure to traumatic events during childhood increases the risk of adult psychopathology, including anxiety, depression, alcohol use disorders and their co-morbidity. Early life trauma also results in increased symptom complexity, treatment resistance and poor treatment outcomes. The purpose of this study was to establish a novel rodent model of adolescent stress, based on an ethologically relevant life-threatening event, live predator exposure. Rats were exposed to a live predator for 10 min. at three different time points (postnatal day (PND)31, 46 and 61). Adult depression-, anxiety-like behaviors and ethanol consumption were characterized well past the last acute stress event (two weeks). Behavioral profiles across assessments were developed to characterize individual response to adolescent stress. CNS activation patterns in separate groups of subjects were characterized after the early (PND31) and last predator exposure (PND61). Subjects exposed to live-predator adolescent stress generally exhibited less exploratory behavior, less propensity to venture into open spaces, a decreased preference for sweet solutions and decreased ethanol consumption in a two-bottle preference test. Additional studies demonstrated blunted cortisol response and CNS activation patterns suggestive of habenula, rostromedial tegmental (RMTg), dorsal raphe and central amygdala involvement in mediating the adult consequences of adolescent stress. Thus, adolescent stress in the form of live-predator exposure results in significant adult behavioral and neurobiological disturbances. Childhood trauma, its impact on neurodevelopment and the subsequent development of mood disorders is a pervasive theme in mental illness. Improving animal models and our neurobiological understanding of the symptom domains impacted by trauma could significantly improve treatment strategies.

Fenología de Crescentia alata (Bignoniaceae) en Guanacaste, Costa Rica

Los estudios fenológicos generan información que contribuye con el conocimiento de las relaciones entre especies y componentes abióticos de los ecosistemas, disponibilidad de alimento para animales y regeneración de cobertura boscosa. Crescentia alata es una especie arbórea abundante en el bosque tropical seco (BTs); su importancia ecológica, cultural y económica ha sido ampliamente reconocida y por eso existe interés en reproducir esta especie, pero antes es necesario conocer detalladamente su desarrollo fenológico. El objetivo de este estudio fue describir la fenología de C. alata en el BTs de Costa Rica. Se seleccionaron 20 árboles reproductivos en el Parque Nacional Santa Rosa para observar las siguientes fenofases: follaje, floración y fructificación por 14 meses entre 2015 y 2016. Esta especie produjo más follaje en junio, máxima floración en junio y octubre y mayor número de frutos maduros en enero. Los patrones fenológicos en C. alata se relacionaron con factores climáticos comunes, sobre todo precipitación, temperatura y humedad relativa. Los resultados más relevantes de este estudio podrían contribuir a la propagación, el manejo adecuado y la conservación de esta especie.

Phenological studies generate information that contributes knowledge on relationships of species and abiotic components of ecosystems, availability of food for animals and regeneration of forest cover. Crescentia alata is an abundant tree species in tropical dry forests; its ecological, cultural and economic importance has been widely recognized and for this reason there is an interest in reproducing this species, but previously it is necessary to understand its detailed phenological development. The aim of this work was to describe C. alata phenology in dry Costa Rican forests. Twenty reproductive trees were selected at the Santa Rosa National Park to observe phenophases (leaf flushing, flower production, and fructification) during 14 months from 2015 to 2016. Most foliage was observed in June, maximal floration in June and October, and the highest ripe-fruit number in January. Phenological patterns in C. alata were related to common climatic factors as rainfall, temperature, and relative humidity; other factors considered were wind speed, and sun radiation. The most significant phenological data registered for C. alata in this work may contribute to a better management and conservation of this species.

Germinación de semillas de Crescentia alata (Bignoniaceae) en distintas condiciones de temperatura, luminosidad y almacenamiento

Crescentia alata (Bignoniaceae) es una especie arborescente de gran interés cultural y económico desde México hasta Costa Rica. Sin embargo, la protección de las poblaciones naturales y el establecimiento de plantaciones son limitados por la carencia de información sobre germinación de semillas y crecimiento de plántulas. Este estudio pretende caracterizar los frutos y las semillas, evaluar el proceso de germinación a diferentes temperaturas y niveles de luminosidad, y determinar las condiciones óptimas de temperatura, humedad y almacenamiento para mantener viables las semillas. Se midieron altura, diámetro y masa de frutos, así como largo, ancho y masa de semillas; además, se contó el número de semillas por fruto. Asimismo, se evaluó el porcentaje de germinación a cinco temperaturas (15, 20, 30, 20-30 y 25-30 °C), en condiciones de luz-oscuridad, con almacenamiento a tres temperaturas (5° C, 15 °C y ambiente: 22-24 °C) durante 36 meses. También se observó la viabilidad de las semillas conservadas dentro del fruto. El valor promedio del índice de redondez (IR) fue -1.86; esto indica que los frutos son redondeado-achatados. En promedio el fruto midió 7.90 ± 2.58 cm de altura y 9.62 ± 1.21 cm de diámetro; las semillas midieron 0.75 ± 0.07 cm de largo y 0.67 ± 0.05 cm de ancho. La masa promedio del fruto fue 414.57 g y cada fruto tuvo en promedio ca. 691 semillas, que no germinaron a 15 °C ni a 20 °C; en la oscuridad disminuyó la germinación y la viabilidad de las semillas se redujo cuando se almacenaron a temperatura ambiente (22-24 °C) y cuando permanecieron dentro del fruto. Los resultados indican que las semillas de C. alata germinan mejor a 30 °C, en condiciones de luz y separadas de la pulpa del fruto antes de almacenarse; además, almacenadas a temperaturas bajas (5 °C y 15 °C) los porcentajes de germinación y la viabilidad se mantienen altos (ca. 90 %) hasta por tres años. Estos datos pueden contribuir a mejorar el almacenamiento de semillas y la obtención de plántulas para propagación; así podría aumentar el tamaño de las poblaciones con fines económicos o de conservación, lo que favorecería tanto a la especie estudiada como al bosque tropical seco en que habita.

Crescentia alata is a natural resource with cultural and economic value from Mexico to Costa Rica. Nevertheless, protection of natural populations and establishment of plantations are limited by lack of information on seed germination and plant growth. This study aims to characterize size, weight and number of fruits and seeds, to evaluate the seed germination process at different temperatures and light conditions, and to determine the optimal conditions of temperature, humidity, and storage periods for viable seeds. We measured germination at five different temperatures (15, 20, 30, 20-30, and 25-30 °C), in light-dark conditions, with seed storage at three temperatures (5 °C, 15 °C, and ambient temperature: 22-24 °C) during 36 months. Mean values: fruit roundness index -1.86 (i.e. they are flattened-rounded). Fruit height 7.90 ± 2.58 cm, diameter 9.62 ± 1.21 cm; seeds were 0.75 ± 0.07 cm long and 0.67 ± 0.05 cm wide. Fruit mass 414.57 g; each fruit contained on average ca. 691 seeds. Seeds did not germinate at 15 °C or 20 °C; germination decreased in darkness; germination and viability decreased when seeds were stored at ambient temperature (22-24 °C), and when they were preserved inside fruits. The seeds of C. alata germinate better at 30 °C, exposed to light, and separated from the pulp before storage. When seeds are stored at low temperatures (5 °C and 15 °C), high germination and viability percentages (ca. 90 %) can be maintained for three years, allowing conservation programs for the species.

Efecto del almacenamiento ex situ de semillas y de condiciones lumínicas sobre la tasa de crecimiento de plántulas de Crescentia alata (Bignoniaceae)

En el bosque tropical seco, el árbol Crescentia alata (Bignoniaceae) es un recurso cultural y económico, pero han fracasado algunos intentos para establecer plantaciones, que podrían satisfacer la producción comercial y, así, evitar el impacto en las poblaciones naturales. Por tanto, existe la necesidad de generar información biológica sobre esta especie para obtener plantas en condiciones de invernaderos. El objetivo de este trabajo fue evaluar la tasa de crecimiento de plantas de C. alata obtenidas de semillas que se almacenaron en diferentes períodos y a varias temperaturas, y determinar el efecto de la intensidad de la luz sobre el crecimiento de las plántulas. Se recolectaron frutos en Liberia (Guanacaste, Costa Rica) y se almacenaron semillas por 0, 4, 8 y 14 meses a 5 °C, 15 °C y a temperatura ambiente (22-24 °C). Las plántulas de las semillas almacenadas por 0, 4, 8 y 14 meses se trasplantaron para evaluar el crecimiento después de 8 días, 2 y 16 meses, y en dos condiciones de luminosidad. La morfología de las plántulas de 8 días cambió según el tiempo de almacenamiento. El análisis de componentes principales de la evaluación de 2 meses indica que las variables más significativas fueron biomasa total seca, biomasa seca de hojas, de raíz-vástago, de tallo y de raíz, mientras que en el análisis de la evaluación de 16 meses tales variables fueron biomasa seca de raíz, de raíz-vástago y de hojas, también número de hojas y longitud del vástago. El área foliar específica de plantas con 16 meses de edad obtenidas de semillas almacenadas 14 meses no cambió con la temperatura de almacenamiento. Además, dos condiciones de luminosidad influyeron en la altura, el diámetro del tallo o el número de hojas. El almacenamiento de semillas a 5 °C y 15 °C favoreció el desarrollo de los cotiledones, así como la longitud de la raíz y del hipocótilo. Plantas de 2 meses obtenidas de 0 y 8 meses asignaron mayor biomasa a raíces que a tallos, mejorando así la absorción de agua. Plantas de 16 meses provenientes de semillas no almacenadas desarrollaron el mayor número de hojas, y aquellas de semillas de 8 meses a 5 °C y 15 °C mostraron tallos más cortos. Las semillas almacenadas hasta 14 meses se convirtieron en plantas bien desarrolladas. Se recomienda a futuros investigadores evaluar la viabilidad a diferentes temperaturas de secado de las semillas y en niveles de intensidad lumínica más contrastantes durante el crecimiento.

The dry tropical forest tree Crescentia alata is a cultural and economical resource, but efforts to establish plantations, which could satisfy commercial production and avoid impact on natural populations, have been unsuccessful. So there is a need to generate biological information on this species for obtaining plants in greenhouses. The aim of this work was to evaluate the vigor and growth rate of C. alata seedlings born from seeds that were stored at different periods and temperatures, and to determine the effect of light intensity on the seedlings. Fruits were collected in Liberia (Guanacaste, Costa Rica) and seeds stored for 0, 4, 8, and 14 months at 5 °C, 15 °C, and ambient temperature (22-24 °C). Seedlings from seeds stored for 0, 4, 8 and 14 months were grown to evaluate growth after 8 days, 2 months, and 16 months, and in two different light conditions. Morphology of 8-day-seedlings changed according to storage time. Principal component analysis of 2-month evaluation indicates that the most significant variables were total dry biomass, dry biomass of leaves, root-shoot, stem, and root, while for the analysis of 16-month evaluation these variables were dry biomass of root, root-shoot, and leaves, also leaf number, and shoot length. Specific leaf area of 16-month plants from seeds stored for 14 months did not change with storage temperature. In addition, two different light conditions influence seedling height, stem diameter or leaf number. Seed storage at 5 °C and 15 °C favored development of seedling cotyledons, and length of both root and hypocotyl. Two month-seedlings from 0M and 8M allocated most biomass to roots and less to stems, enhancing this way water absorption. Sixteen-month-plants from non-stored seeds developed the highest leaf numbers, and those plants from 8M seeds at 5 °C and 15 °C showed shorter stems. Seeds stored up to 14 months kept viable, becoming healthy seedlings. We recommend that future researchers evaluate seed viability at different drying temperatures and more contrasting light levels.

The rostromedial tegmental nucleus modulates the development of stress-induced helpless behavior.

A growing body of clinical and preclinical research suggests that structural and functional changes in the habenula, a component of the epithalamus, are associated with major depressive disorder. A major excitatory, efferent projection from the habenula targets the rostromedial tegmentum (RMTg), a mesopontine region that provides significant input to the ventral tegmentum and raphe nuclei. While the RMTg contributes to monoaminergic responses to aversive events, its role in stress-based animal models of depression has yet to be determined. In the present study, we test the hypothesis that the RMTg is a component of the circuitry mediating the development of a maladaptive behavior in which rats repeatedly exposed to inescapable footshock, fail to avoid or escape the same stressor when subsequently given the opportunity to do so. Excitotoxic lesions of the RMTg significantly diminished the frequency of these escape failures 24 h after exposure to inescapable footshock. Conversely, electrical stimulation of the Hb during the initial uncontrollable aversive event, a manipulation that enhances excitatory input to the RMTg, increased the number of trials in which subjects failed to escape an aversive stimulus when presented the option 24 h later. These complementary results provide evidence supporting a role for the RMTg in the expression of stress-induced helpless phenotype and are an important step in understanding the contribution made by this region to the development of depression-related maladaptive behaviors.

Trastornos por uso de sustancias ytrastorno por déficit de atención e hiperactividad: frecuencia en pacientesvarones hospitalizados en un servicio de adicciones / Substance use disorders and attention-deficit/hyperactivity disorder: frequency in male patients at an specializedaddictions hospital ward

Los Trastornos por Uso de Sustancias (TUS) son un grave problema de salud pública. El Trastorno por Déficit de Atención e Hiperactividad (TDAH) es una comorbilidad asociada con el inicio y pronóstico del TUS. Objetivos: determinar la frecuencia de TDAH en pacientes varones con TUS hospitalizados en un servicio de adicciones altamente especializado Métodos: se evaluó el diagnóstico de TDAH en412 historias clínicas de pacientes dependientes a sustancias psicoactivas hospitalizados en el Servicio de Adicciones del Hospital Hermilio Valdizán, durante el año 2011 y 2012. Se utilizó elCIE-10 para la clasificación diagnóstica. Resultados: se encontró que el 72,57% presentaban algún tipo de comorbilidad psiquiátrica. El 29,37% de la población total cumplía criterios para TDAH comórbido. Conclusiones: el trastorno por déficit de atención e hiperactividad está presente en tres de cada diez pacientes con TUS. El análisis primario del presente estudio parece encontrar una posible relación entre TUS y el TDAH.

Substance use disorders (SUD) are a severe public health problem. Attention-deficit hyperactivity disorder (ADHD) is a comorbidity associated to the onset and prognosis of SUD. Objectives: To determinate the prevalence of ADHD in SUD men patients hospitalized in a highly specialized mental health institution. Methods: ADHD diagnosis was evaluated in 412clinical histories of patients with dependence to psychoactive substances that were hospitalized on Hermilio Valdizan Hospital´s Addiction Service, in 2011 and 2012. The ICD-10 diagnostic criteria was used. Results: The 72.57% of the patients presented psychiatric comorbidity. Overall, 29.37% of all SUD patients accomplished ICD-10 criteria for comorbid ADHD. Conclusions: ADHD is present in three out of ten patients with SUD. The primary analysis of this study suggests a relation between the dependency to psychoactive substances and comorbid ADHD.

Therapeutic hypothermia: critical review of the molecular mechanisms of action.

Therapeutic hypothermia (TH) is nowadays one of the most important methods of neuroprotection. The events that occur after an episode of ischemia are multiple and hypothermia can affect the various steps of this cascade. The mechanisms of action of TH are varied and the possible explanation for the benefits of this therapy is probably the multiple mechanisms of action blocking the cascade of ischemia on many levels. TH can affect many metabolic pathways, reactions of inflammation, apoptosis processes, and promote neuronal integrity. To know the mechanisms of action of TH will allow a better understanding about the indications for this therapy and the possibility of searching for other therapies when used in conjunction with hypothermia will provide a therapeutic synergistic effect.

Disruption of conditioned reward association by typical and atypical antipsychotics.

Antipsychotic drugs are broadly classified into typical and atypical compounds; they vary in their pharmacological profile however a common component is their antagonist effects at the D2 dopamine receptors (DRD2). Unfortunately, diminished DRD2 activation is generally thought to be associated with the severity of neuroleptic-induced anhedonia. The purpose of this study was to determine the effect of the atypical antipsychotic olanzapine and typical antipsychotic haloperidol in a paradigm that reflects the learned transfer of incentive motivational properties to previously neutral stimuli, namely autoshaping. In order to provide a dosing comparison to a therapeutically relevant endpoint, both drugs were tested against amphetamine-induced disruption of prepulse inhibition as well. In the autoshaping task, rats were exposed to repeated pairings of stimuli that were differentially predictive of reward delivery. Conditioned approach to the reward-predictive cue (sign-tracking) and to the reward (goal-tracking) increased during repeated pairings in the vehicle treated rats. Haloperidol and olanzapine completely abolished this behavior at relatively low doses (100microg/kg). This same dose was the threshold dose for each drug to antagonize the sensorimotor gating deficits produced by amphetamine. At lower doses (3-30microg/kg) both drugs produced a dose-dependent decrease in conditioned approach to the reward-predictive cue. There was no difference between drugs at this dose range which indicates that olanzapine disrupts autoshaping at a significantly lower proposed DRD2 receptor occupancy. Interestingly, neither drug disrupted conditioned approach to the reward at the same dose range that disrupted conditioned approach to the reward-predictive cue. Thus, haloperidol and olanzapine, at doses well below what is considered therapeutically relevant, disrupts the attribution of incentive motivational value to previously neutral cues. Drug effects on this dimension of reward processing are an important consideration in the development of future pharmacological treatments for schizophrenia.

Cognitive effects of psychotomimetic drugs in rats discriminating number cues.

RATIONALE: Deficits in memory and attention are broadly acknowledged during psychosis; however, experiments on modeled psychosis often test working memory without systematic manipulation of attentional demands. OBJECTIVES: The major research goal was discovering which neurobehavioral processes, attention, or memory contributed more to drug-provoked performance deficits. MATERIALS AND METHODS: Rats were trained to perform operant ratio discrimination (RD) tasks wherein the number of presses at a rear-wall lever was discriminated using one of two front-wall levers. Effects from four psychotomimetic drugs, the serotonin agonist 2,5-dimethoxy-4-iodoamphetamine, the noncompetitive NMDA-glutamate receptor antagonist phencyclidine (PCP), and two CB1-selective cannabinoid agonists, WIN 55,512-2 and AM 411, were assessed using a signal detection analytical overlay to dissociate cognitive from noncognitive motor and motivational disruptions. Further methods allowed dissociation of attention compromises from mnemonic deficits. RESULTS: For each test compound, at least one dose elicited decreased RD accuracy without affecting response rates, and task difficulty was shown to be a crucial dictator of accuracy effect specificities. Effects from both PCP and WIN 55,512-2 biased animals to select the response lever conditioned for denser reinforcement. The same two drugs rendered peculiar response patterns in distracter light session components, considering light blinks were included to divert subjects' attention away from task-relevant information. The response patterns determined during distracter components of PCP/WIN testing sessions, counterintuitively, suggest performance enhancement. CONCLUSION: Comprehensive viewing of RD performance patterns after drug administration indicates that sustained attention and transient information management are significantly impaired during the drug-induced psychosis state, while selective attention is less affected.

Brain stimulation and morphine reward deficits in dopamine D2 receptor-deficient mice.

RATIONALE: The rewarding effects of lateral hypothalamic brain stimulation, various natural rewards, and several drugs of abuse are attenuated by D1 or D2 dopamine receptor (D1R or D2R) antagonists. Much of the evidence for dopaminergic involvement in rewards is based on pharmacological agents with limited or "relative" selectivity for dopamine receptor subtypes. Genetically engineered animal models provide a complementary approach to pharmacological investigations. OBJECTIVES: In the present study, we explored the contribution of dopamine D2Rs to (1) brain stimulation reward (BSR) and (2) the potentiation of this behavior by morphine and amphetamine using D2R-deficient mice. METHODS: Wild-type (D2Rwt), heterozygous (D2Rhet), and D2R knockout (D2Rko) mice were trained to turn a wheel for rewarding brain stimulation. Once equivalent rate-frequency curves were established, morphine-induced (0, 1.0, 3.0, and 5.6 mg/kg s.c.) and amphetamine-induced (0, 1.0, 2.0, and 4.0 mg/kg i.p.) potentiations of BSR were determined. RESULTS: The D2Rko mice required approximately 50% more stimulation than the D2Rwt mice did. With the equi-rewarding levels of stimulation current, amphetamine potentiated BSR equally across the three genotypes. In contrast, morphine potentiated rewarding stimulation in the D2Rwt, had no effect in the D2Rhet, and antagonized rewarding stimulation in the D2Rko mice. CONCLUSIONS: D2R elimination decreases, but does not eliminate, the rewarding effects of lateral hypothalamic stimulation. After compensation for this deficit, amphetamine continues to potentiate BSR, while morphine does not.

Texture of locomotor path: a replicable characterization of a complex behavioral phenotype.

A database of mouse locomotor path in spatial tests can be used to search in silico for behavioral measures that better discriminate between genotypes and are more replicable across laboratories. In this study, software for the exploration of exploration (SEE) was used to search a large database for a novel behavioral measure that would characterize complex movement paths. The database included mouse open-field behavior assessed in 3 laboratories, 7 inbred strains, several pharmacological treatments and hundreds of animals. The new behavioral measure, "path texture", was characterized using the local curvature of the path (the change of direction per unit distance, in degrees/cm) across several spatial scales, starting from scales smaller than the animal's body length and up to the scale of the arena size. Path texture analysis differs from fractal dimension analysis in that it does not assume self-similarity across scales. Path texture was found to discriminate inbred strains with relatively high broad-sense heritability (43%-71%) and high replicability across laboratories. Even genotypes that had similar path curvatures in some scales usually differed in other scales, and self-similarity across scales was not displayed by all genotypes. Amphetamine decreased the path curvature of C57BL/6 mice in small and medium scales, while having no effect on DBA/2J mice. Diazepam dose-dependently decreased the curvature of C57BL/6 mice across all scales, while 2 anxiogenic drugs, FG-7142 and pentylenetetrazole, increased it. Path texture thus has high potential for behavioral phenotyping and the study of drug effects in the mouse.

Fenología de árbol Sideroxylon capiri (Sapoteceae) en el Bosque Seco Tropical de Costa Rica / Phenology of the tree Sideroxylon capiri (Sapotaceae) at the tropical dry forest in Costa Rica

From March 1996 until February 2000, an study about the phenology of the Tempisque tree [Sideroxylon capiri (A.DC.) Pittier ] was made in the Tropical Dry Forest of the Barra Honda National Park (Costa Rica).Ten trees were choosen at random and their phenology was evaluated monthly during the first two years and every two months afterwards. Climatological data were also collected in situ .Trees change their foliage each year during the rainy season or at the beginning of the dry season. In contrast with other native species in forest, soil water deficit is not responsible for foliage change in S.capiri. Some elements that affect the process are photoperiod and herbivores. Unknown physiological mechanisms allow the tree to maintain foliage during the driest months (March and April). Flowering and fruiting may occur every year and in any season,but mostly in the dry season, with variability both among seasons and among individuals

Se estudió la fenología del árbol de tempisque Sideroxylon capiri (A.DC.) Pittier en el Bosque Seco Tropical del Parque Nacional Barra Honda (Costa Rica), desde marzo de 1996 hasta febrero de 2000. Para ello se tomaron diez árboles escogidos al azar, a los cuales se les evaluó la fenología, una vez al mes durante los dos primeros años y posteriormente cada dos meses. Además, se tomaron datos climatológicos in situ para establecer relaciones con el comportamiento fenológico. Se encontró que los árboles renuevan el follaje cada año, pero la caída ocurre durante el período lluvioso o a inicios del seco, por lo que, contrario a lo que sucede en otras especies nativas de este tipo de bosque, el déficit hídrico del suelo no es el responsable de la caída del follaje, sino que deben haber otros factores ambientales responsables de ello. Entre estos podrían estar el fotoperíodo y la presencia de herbívoros. Durante los meses más secos (marzo y abril)todos los árboles mantienen su follaje al máximo y para que esto ocurra deben existir también mecanismos fisiológicos particulares. Respecto a los procesos de floración y fructificación, estos se presentan todos los años, especialmente en el período de sequía, pero es posible que ocurran en cualquier otra época del año. Existen diferencias en la magnitud de la floración y fructificación, dependiendo de la época y del individuo. Se discuten las posibles causas de este comportamiento fenológico, así como las ventajas ecológicas que podría tener

[Phenology of the tree Sideroxylon capiri (Sapotaceae) at the tropical dry forest in Costa Rica]. / Fenologia de árbol Sideroxylon capiri (Sapotaceae) en el Bosque Seco Tropical de Costa Rica.

From March 1996 until February 2000, an study about the phenology of the Tempisque tree [Sideroxylon capiri (A.DC.) Pittier] was made in the Tropical Dry Forest of the Barra Honda National Park (Costa Rica). Ten trees were chosen at random and their phenology was evaluated monthly during the first two years and every two months afterwards. Climatological data were also collected in situ. Trees change their foliage each year during the rainy season or at the beginning of the dry season. In contrast with other native species in forest, soil water deficit is not responsible for foliage change in S. capiri. Some elements that affect the process are photoperiod and herbivores. Unknown physiological mechanisms allow the tree to maintain foliage during the driest months (March and April). Flowering and fruiting may occur every year and in any season, but mostly in the dry season, with variability both among seasons and among individuals.

Altered prepulse inhibition in rats treated prenatally with the antimitotic Ara-C: an animal model for sensorimotor gating deficits in schizophrenia.

RATIONALE: Sensorimotor gating disruption is one of many neurocognitive deficits seen in schizophrenia. Disorganized thought is one of the cardinal symptoms associated with sensorimotor gating. In an attempt to model sensorimotor gating deficits in rats relevant to the neurodevelopmental hypothesis for schizophrenia, we have used prenatal injections of the antimitotic drug, cytosine arabinoside (Ara-C) to subtly perturb the development of the rat CNS and disrupt sensorimotor gating. OBJECTIVE: To produce rats with either basal sensorimotor gating deficits or increased vulnerability to the disruption of sensorimotor function by apomorphine or phencyclidine (PCP). Prepulse inhibition (PPI) of the acoustic startle response was used to assess sensorimotor gating. METHODS: Three different cohorts of pregnant Sprague Dawley female rats were injected with Ara-C (30 mg/kg in saline) or saline at embryonic days 19.5 and 20.5. The Ara-C and control rats were tested for acoustic startle response and PPI at preadolescent and post-adolescent ages; postnatal day (Pnd) 35 and 56, respectively. Apomorphine (2.0 mg/kg) or phencyclidine (3.0 mg/kg), was given prior to PPI sessions in order to disrupt PPI. RESULTS: At Pnd 35, Ara-C treatment did not significantly affect acoustic startle amplitudes or PPI. However, at PND 56, Ara-C treated rats had significantly lower acoustic startle amplitudes and significantly diminished sensorimotor gating. Pharmacological challenge with the dopamine agonist apomorphine and the glutamate antagonist PCP significantly disrupted sensorimotor gating in the control subjects. Apomorphine did not further disrupt the existing deficit in the Ara-C treated rats. Ara-C treatment did not cause gross loss of neuronal tissue, although there was a subtle and variable disorganization of the pyramidal cell layer in the hippocampal CA2/3 region. CONCLUSION: The results provide evidence to suggest that late embryonic exposure to Ara-C disrupts the circuitry involved in mediating PPI. While the dopamine agonist apomorphine caused a significant disruption in the control rats it did not further disrupt the existing deficit in the Ara-C treated rats. These data provide evidence to support the contention that modest neurodevelopmental insults can significantly affect sensorimotor gating processes in an adult onset dependent manner.

Does gastrointestinal Candida albicans prevent ubiquinone absorption?

Ubiquinones (coenzyme Qs (CoQ)) are essential for oxidative phosphorylation in yeasts and humans, although the isomers present in each are different. The human coenzyme Q, CoQ10, is administered orally for the treatment of heart disease and other disorders. Some patients, however, require much higher doses than others to attain a therapeutic CoQ10 blood level. We propose that one possible explanation for this variability is Candida colonization of the GI tract. Many common medical treatments including antibiotics and anti-hyperchlorhydric agents increase the risk of GI tract Candida colonization. Subsequent uptake and utilization of supplemental CoQ10 by the yeast could diminish availability for the human subject. Data from one patient and an in vitro pilot study using two pathogenic strains of C. albicans support this hypothesis. If C. albicans in the GI tract can hinder availability and interfere with therapeutic effects of CoQ10, it could be of clinical significance for large numbers of patients.

Biotherapeutic agents in the treatment of infectious diarrhea.

Biotherapeutic agents offer unique advantages over traditional treatments for infectious diarrhea, and several have been shown to be effective (Table 4). These therapeutic microbial agents are most effective in types of infectious diseases that are associated with a disruption of the normal intestinal microecology (e.g., AAD, C. difficile disease). The impact of biotherapeutic agents on rotaviral diarrhea is of special clinical importance because this is the most common cause of pediatric diarrhea, and there is no defined treatment. Strong efforts need to be made to limit antibiotic exposure in children. Biotherapeutic agents offer a safe and effective nonantibiotic method of treating this important pathogen, especially after the withdrawal of a rotaviral vaccine from the market by the FDA. However, for many biotherapeutic agents, well-done, placebo-controlled trials still are lacking, and not all types of infectious diarrhea respond to these agents. Continued research in this innovative therapeutic area is warranted.

Possible interaction between warfarin and Lycium barbarum L.

OBJECTIVE: To describe a patient who was stabilized on warfarin and developed an elevated international normalized ratio (INR) after drinking a concentrated Chinese herbal tea. Additionally, to determine the effect of the tea on CYP2C9, the isoenzyme responsible for the metabolism of S-warfarin. CASE SUMMARY: An elevated INR of 4.1 was observed in a 61-year-old Chinese woman, previously stabilized on anticoagulation therapy (INR 2-3). With no changes in her other medications or lifestyle, a review of her dietary habits revealed four days of drinking a concentrated Chinese herbal tea made from Lycium barbarum L. fruits (3-4 glasses daily) prior to her clinic visit Warfarin was withheld for one day and then resumed at a lower weekly dose. She discontinued the tea, while maintaining consistency with medications and dietary habits. A follow-up INR seven days later was 2.4, and seven subsequent INR values were in the 2.0-2.5 range. DISCUSSION: L barbarum L. (family Solanaceae) is a commonly used Chinese herb considered to have a tonic effect on various organs. Any impact of an herbal product on the metabolism of S-warfarin, the enantiomer responsible for most of the anticoagulant activity, could alter the INR values. An herbal-drug interaction was suspected in this case. In vitro evaluation showed inhibition of S-warfarin metabolism by CYP2C9 by the tea of L. barbarum L.; however, the inhibition observed was weak, with a dissociation constant (Ki) value of 3.4 mg/mL, suggesting that the observed interaction may be caused by factors other than the CYP450 system. CONCLUSIONS: There is a potential herbal-drug interaction between warfarin and L. barbarum L., based on an increased INRvalue noted with concurrent use. Thus, combination of L. barbarum L. and warfarin should be avoided. Vigilance is needed with other herbal combinations taken with drugs of narrow therapeutic indices.

Rats and mice share common ethologically relevant parameters of exploratory behavior.

Detailed studies of rat exploratory behavior reveal that it consists of typical behavior patterns having a distinct structure. Recently we have developed interactive software that uses as input the automatically digitized time-series of the animal's location for the visualization, analysis, capturing and quantification of these patterns. We use this software here for the study of BALB/cJtau mouse behavior. The results suggest that a considerable number of rat patterns are also present in the mouse. These ethologically-relevant patterns have a significant potential as a phenotyping tool.

Controlling the false discovery rate in behavior genetics research.

The screening of many endpoints when comparing groups from different strains, searching for some statistically significant difference, raises the multiple comparisons problem in its most severe form. Using the 0.05 level to decide which of the many endpoints' differences are statistically significant, the probability of finding a difference to be significant even though it is not real increases far beyond 0.05. The traditional approach to this problem has been to control the probability of making even one such error--the Bonferroni procedure being the most familiar procedure achieving such control. However, the incurred loss of power stemming from such control led many practitioners to neglect multiplicity control altogether. The False Discovery Rate (FDR), suggested by Benjamini and Hochberg [J Royal Stat Soc Ser B 57 (1995) 289], is a new, different, and compromising point of view regarding the error in multiple comparisons. The FDR is the expected proportion of false discoveries among the discoveries, and controlling the FDR goes a long way towards controlling the increased error from multiplicity while losing less in the ability to discover real differences. In this paper we demonstrate the problem in two studies: the study of exploratory behavior [Behav Brain Res (2001)], and the study of the interaction of strain differences with laboratory environment [Science 284 (1999) 1670]. We explain the FDR criterion, and present two simple procedures that control the FDR. We demonstrate their increased power when used in the above two studies.

Natural segmentation of the locomotor behavior of drug-induced rats in a photobeam cage.

Recently, Drai et al. (J Neurosci Methods 96 (2000) 119) have introduced an algorithm that segments rodent locomotor behavior into natural units of 'staying in place' (lingering) behavior versus going between places (progression segments). This categorization, based on the maximum speed attained within the segment, was shown to be intrinsic to the data, using the statistical method of Gaussian Mixture Model. These results were obtained in normal rats and mice using very large (650 or 320 cm) circular arenas and a video tracking system. In the present study, we reproduce these results with amphetamine, phencyclidine and saline injected rats, using data measured by a standard photobeam tracking system in square 45 cm cages. An intrinsic distinction between two or three 'gears' could be shown in all animals. The spatial distribution of these gears indicates that, as in the large arena behavior, they correspond to the difference between 'staying in place' behavior and 'going between places'. The robustness of this segmentation over arena size, different measurement system and dose of two psychostimulant drugs indicates that this is an intrinsic, natural segmentation of rodent locomotor behavior. Analysis of photobeam data that is based on this segmentation has thus a potential use in psychopharmacology research.